The researchers present the first integrative catalogue of 267 cullin–RING substrate receptors, of which 93 are linked to germline disorders.

The most frequent substrate receptor (SR)-related diseases are neurodevelopmental, neuromuscular, and congenital organ/skeletal syndromes.

Disease associations are shaped by substrate context rather than tissue enriched expression.

Pathogenicity arises through altered degron recognition, disrupted complex assembly, dosage imbalance, or ubiquitin–proteasome system-independent functions.

Distinct variants in the same SR can yield divergent phenotypes, reflecting dosage sensitivity and developmental context.

Patient alleles inform diagnosis and therapeutic strategies, positioning SRs as central nodes connecting proteostasis, rare-disease genetics, and targeted protein degradation. sciencenewshighlights ScienceMission https://sciencemission.com/Cullin%E2%80%93RING-receptors

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Priti Agarwal, Ronen Zaidel-Bar et al. define the stage-specific gene expression programs of a leader cell that drives collective tissue invasion during organ development, identifying membrane trafficking as a central regulator of leader cell behavior.

Migration.

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Collective cell invasion underlies organ development, epithelial repair, and cancer metastasis. “Leader cells” remodel ECM, sense guidance cues, reorganize their cytoskeleton, and coordinate follower cells, but the molecular programs enabling these functions remain unclear. Here, we present a stage-specific transcriptomic dataset of the Caenorhabditis elegans gonadal leader cell, the distal tip cell (DTC), which invades basement membrane and guides germ cells to form U-shaped gonadal arms. Comparing invasive larval-stage DTCs with noninvasive adult-stage DTCs defines the molecular signature of an actively invading leader cell in vivo. Our dataset recapitulates known regulators of gonad morphogenesis and reveals numerous uncharacterized genes with potential roles in leader cell activity. Demonstrating dataset utility, we identify vesicular trafficking proteins enriched in invading DTCs and demonstrate their importance for gonad development using endogenous tagging and DTC-specific RNAi. We also catalog diverse DTC-specific knockdown phenotypes. This resource establishes a molecular framework for leader cell activity and a platform to investigate conserved mechanisms of invasive migration.

A new form of in vivo CAR-T therapy kills leukemia, multiple myeloma, and sarcoma in mice, opening the door to a future off-the-shelf cancer treatment without chemotherapy.

For years, one of the most powerful weapons against certain blood cancers, called CAR-T therapy, has required an elaborate process: Doctors extract a patient’s immune cells, ship them to a specialized facility where they’re genetically reprogrammed to fight cancer, then ship them back for infusion into the patient’s bloodstream. This has revolutionized cancer treatment, but the time and expense place it out of reach for thousands of patients.

Now, scientists at UC San Francisco and UC Berkeley have developed a method to precisely reprogram these cancer-fighting cells directly inside the body, potentially eliminating the barriers that have kept this life-saving therapy out of reach for many patients around the world.

https://doi.org/10.1172/jci.insight.

Here, Tobias B. Huber & team use a state-of-the-art, tour de force experimental design to show LSD1 regulates kidney development, and its dysfunction disrupts key kidney cells, leading to cyst formation in mouse and organoid models.

The image shows severe structural changes in the adult mouse kidney with loss of KDM1a. Nephrology.

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⁴Faculty of Biology, Albert Ludwigs University of Freiburg, Freiburg, Germany.

⁵Institute of Medical Bioinformatics and Systems Medicine and.

⁶Institute of Surgical Pathology, Faculty of Medicine, Medical Center — University of Freiburg, Freiburg, Germany.

Year 2025 This could essentially end disease where the diseases would be edited off and the host repaired internally.

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Scientists identified 473 human genes that act as genetic “on/off switches,” shaping disease risk through tissue-specific or universal patterns regulated by DNA changes and hormones.

Study: Switch-like gene expression modulates disease risk. Image Credit: gopixa / Shutterstock.

In a recent article published in Nature Communications, researchers analyzed methylomes, transcriptomes, and genomes from 943 individuals to characterize and identify genes that exhibit distinct on-off switches and explore their epigenetic and genetic regulation.

Nutrient stress in DNA damage.

The dynamic interplay between nutrient stress and DNA damage governs cellular survival through coordinated regulation of genomic integrity and metabolic adaptation. Nutrient deprivation, such as glucose or amino acid limitation, engages nutrient sensors, including AMPK and mTORC1, to rewire energy homeostasis while directly influencing DNA repair via regulating PARP1, BRCA1, and other core repair machinery.

DNA damage-activated kinases (ATM/ ATR) orchestrate metabolic reprogramming to fuel repair processes, enforcing context-dependent cell fate decisions via cell cycle arrest or apoptosis regulation.

Nutrient stress exacerbates genomic instability through depleting antioxidants, such as NADPH or glutathione (GSH), promoting oxidative DNA lesions that overwhelm repair capacity, while defective DNA repair conversely drives metabolic dysregulation in tumors.

In the future, more efficacious tumor therapeutic strategies propose combining targeted nutrient stress with DNA damage repair inhibitors to exploit synthetic lethality. However, clinical translation requires resolving key challenges including tumor heterogeneity in nutrient stress-response pathways and adaptive metabolic plasticity during therapy sciencenewshighlights ScienceMission https://sciencemission.com/nutrient-stress–and-DNA-damage

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Cells are constantly exposed to various stresses, including nutrient deprivation and genotoxic stress, which dynamically interact with cellular sensing pathways to influence metabolism, gene expression, and homeostasis. The integration of nutrient-sensing mechanisms and DNA damage response pathways is critical in cancer progression. While individual processes are well-characterized, their cross-regulatory mechanisms are just beginning to emerge. Deciphering the interplay between nutrient stress and DNA damage is crucial for elucidating the mechanisms underlying cellular responses to stress and developing therapeutic strategies for various diseases, including cancer. This review highlights the relationship between nutrient stress and DNA damage, especially its underlying sensing pathway and cell fate determination.

Microscopic images of human tissue are a cornerstone of biomedical research and clinical diagnostics. Yet despite their importance, these images often remain difficult to analyze systematically and to connect with other types of biological data. A new study led by CeMM Principal Investigator André Rendeiro and published in Nature Methods introduces “LazySlide,” an open-source software tool that brings the power of foundation models and aims to democratize digital pathology analysis.

Whether it’s an inflamed artery, a tumor spreading into the lung or subtle damage in an organ, when doctors or researchers want to understand what’s happening inside a tissue, one of the most trusted tools is still the microscope. Today, they have largely gone digital: A single tissue sample can be scanned into a whole-slide image so detailed that one can zoom from a bird’s-eye view of the entire tissue down to individual cells. These images, therefore, contain enormous information about tissues from different scales.

However, these images are huge, complex, and often difficult to analyze in a modern, data-driven way. While genetics and single-cell biology have developed effective ways for sharing and comparing data, digital pathology images are hard to incorporate—stored in proprietary formats, processed with incompatible tools, and hard to connect to molecular information like RNA sequencing. Thus, the valuable resources of digitalized tissue images are largely underutilized in many research and clinical settings.